Francisella tularensis (F. tularensis) is a category A bioterrorism agent and is the etiological agent of a multisyndromic disease known as tularemia. Antibiotics are available to treat this disease, but initial diagnosis is difficult. This may lead to recognition delay in the event of a bioterrorist attack with a resultant increase in morbidity. The goal of this proposal is to identify proteins involved in the pathogenic growth cycle of two subspecies of F. tularensis (Type A Schu 4 and Type B live vaccine strain (LVS)). Proteomics is a powerful method to identify modulated proteins. Significant proteome coverage can be achieved in organisms with small, sequenced genomes. This proposal outlines plans to exploit recent genomic and proteomic technical advancements by categorizing protein expression in F. tularensis; especially establishing the protein expression patterns of two strain types, each with distinctive virulence ranges. The result of this project will be the identification, relative quantitation, and cell localization of the majority of protein products produced by F. tularensis in standard broth conditions and after infecting human macrophages. Changes in protein expression patterns will help identify gene products important for F. tularensis pathogenesis. This list of virulence candidates will be shared with the research community for subsequent exploration of the pathology of this organism for the purpose of reducing its lethality as an instrument of bioterrorism.